Muse 细胞被鉴定为多能表面标记 SSEA-3 阳性细胞，是位于骨髓 (BM)、外周血和器官结缔组织中的多能样内源干细胞。然而，胚胎外组织中 SSEA-3( ) 细胞的详细特征尚不清楚。在这里，我们证明，与从 BM、脂肪组织和真皮收集的人成人组织 Muse 细胞 SSEA-3( ) 类似，人脐带 (UC)-SSEA-3( ) 细胞表达多能性标记物、分化在单细胞水平上进入三叶细胞谱系细胞，迁移到受损组织，并表现出低端粒酶活性和非致瘤性。值得注意的是，~20% 的人类 UC-SSEA-3( ) 细胞的 X 失活特异性转录物 (XIST)（一种幼稚多能干细胞特征）呈阴性，而所有人类成体组织 Muse 细胞均为 XIST 阳性。单细胞RNA测序显示，与人成体组织Muse细胞相比，人UC-SSEA-3( )细胞的基因表达谱与人植入后囊胚的基因表达谱更相似。 DNA甲基化水平显示出相同的趋势，并且值得注意的是，与分化特别相关的基因的甲基化水平在人-UC-SSEA-3()细胞中比在人-成体组织-Muse细胞中更低。此外，人UC-SSEA-3()细胞在体外分化诱导后新表达胚胎外、种系和造血谱系特异的标记物，而人成人组织Muse细胞仅对诱导有部分反应。在活体的各种干/祖细胞中，尚未在人类中发现那些表现出与幼稚状态的植入后囊胚相似的特性的细胞。易于获取的人类 UC-SSEA-3( ) 细胞可能是研究人类早期发育和人类生殖医学的宝贵工具。© 2024。作者。

Muse cells, identified as cells positive for the pluripotent surface marker SSEA-3, are pluripotent-like endogenous stem cells located in the bone marrow (BM), peripheral blood, and organ connective tissues. The detailed characteristics of SSEA-3(+) cells in extraembryonic tissue, however, are unknown. Here, we demonstrated that similar to human-adult tissue-Muse cells collected from the BM, adipose tissue, and dermis as SSEA-3(+), human-umbilical cord (UC)-SSEA-3(+) cells express pluripotency markers, differentiate into triploblastic-lineage cells at a single cell level, migrate to damaged tissue, and exhibit low telomerase activity and non-tumorigenicity. Notably, ~ 20% of human-UC-SSEA-3(+) cells were negative for X-inactive specific transcript (XIST), a naïve pluripotent stem cell characteristic, whereas all human adult tissue-Muse cells are XIST-positive. Single-cell RNA sequencing revealed that the gene expression profile of human-UC-SSEA-3(+) cells was more similar to that of human post-implantation blastocysts than human-adult tissue-Muse cells. The DNA methylation level showed the same trend, and notably, the methylation levels in genes particularly related to differentiation were lower in human-UC-SSEA-3(+) cells than in human-adult tissue-Muse cells. Furthermore, human-UC-SSEA-3(+) cells newly express markers specific to extraembryonic-, germline-, and hematopoietic-lineages after differentiation induction in vitro whereas human-adult tissue-Muse cells respond only partially to the induction. Among various stem/progenitor cells in living bodies, those that exhibit properties similar to post-implantation blastocysts in a naïve state have not yet been found in humans. Easily accessible human-UC-SSEA-3(+) cells may be a valuable tool for studying early-stage human development and human reproductive medicine.© 2024. The Author(s).